Ephron was born in New York City to a Jewish family, the eldest of four daughters, and grew up in Beverly Hills.[4] Her parents, Henry and Phoebe Ephron (née Wolkind), were both East Coast-born and were noted playwrights and screenwriters. Nora's sisters Delia and Amy are also screenwriters. Her sister Hallie Ephron is a journalist, book reviewer, and novelist who writes crime fiction. Ephron's parents based the ingenue character in the play and film version of Take Her, She's Mine on the 22-year-old Nora and her letters from college.[5] Both her parents became alcoholics during their declining years.[4] Ephron graduated from Beverly Hills High School in 1958, and from Wellesley College in Wellesley, Massachusetts, in 1962.

She was married three times. Her first marriage, to writer Dan Greenburg, ended in divorce after nine years.[4] In 1976, she married journalist Carl Bernstein of Watergate fame. In 1979, Ephron had a toddler son, Jacob, and was pregnant with her second son Max when she discovered Bernstein's affair with their mutual friend,[6] married British politician Margaret Jay. Ephron was inspired by this to write the 1983 novel Heartburn,[7] which was then made into a 1986 Mike Nichols film starring Jack Nicholson and Meryl Streep. In the book, Ephron wrote of a husband named Mark, who was "capable of having sex with a Venetian blind."[4] She also wrote that the character Thelma (based on Margaret Jay) looked like a giraffe with "big feet."[4] Bernstein threatened to sue over the book and film, but he never did.[5]

Ephron was married for more than 20 years to screenwriter Nicholas Pileggi until her death. The couple lived in New York City.

Although Jewish by birth, Ephron was not religious. "You can never have too much butter – that is my belief. If I have a religion, that's it," she quipped in an NPR interview about her 2009 movie, Julie & Julia.[8]

Her son Jacob Bernstein directed an HBO movie on her life called Everything Is Copy.[9]

After eventually quitting Newsweek because she was not allowed to write there, Ephron participated in a class action lawsuit against the magazine for sexual discrimination, described in the book Good Girls Revolt: How the Women of Newsweek Sued Their Bosses and Changed the Workplace by Lynn Povich, and both the lawsuit and Ephron’s role were fictionalized in a 2016 Amazon series by the same main title.[12]

After a satire she wrote lampooning the New York Post caught the editor's eye, Ephron landed a job at the Post, where she stayed as a reporter for five years.[5] In 1966, she broke the news in the Post that Bob Dylan had married Sara Lownds in a private ceremony three-and-a-half months before.[13] Upon becoming a successful writer, she wrote a column on women's issues for Esquire.[4] In this position, Ephron made a name for herself by taking on subjects as wide-ranging as Dorothy Schiff, her former boss and owner of the Post; Betty Friedan, whom she chastised for pursuing a feud with Gloria Steinem; and her alma mater Wellesley, which she said had turned out "a generation of docile and unadventurous women."[5] A 1968 send-up of Women's Wear Daily in Cosmopolitan resulted in threats of a lawsuit from WWD.[5]

She rewrote a script for All the President's Men, in the mid-1970s, along with her then husband Bernstein. While that script was not ultimately used, it was seen by someone who offered Ephron her first screenwriting job, for a television movie,[5] which began her prolific screenwriting career.

For many years, Ephron was among only a handful of people in the world who knew the true identity of Deep Throat, the source for news articles written by her ex-husband Carl Bernstein and Bob Woodward during the Watergate scandal.[15] Ephron said she guessed the identity of Deep Throat after reading Bernstein's notes, which referred to the unnamed person as "MF."[15] Bernstein claimed "MF" was short for "My Friend," but Ephron guessed correctly that the initials stood for Mark Felt, the late former associate director of the FBI. Until Felt said in 2005 that he was Deep Throat, there was much speculation about who Bernstein and Woodward's source was.[15]

Ephron's marriage with Bernstein ended acrimoniously, and after the breakup Ephron was open about the identity of Deep Throat.[4] She revealed his identity to her son Jacob and anyone else who asked. She once commented, "I would give speeches to 500 people and someone would say, 'Do you know who Deep Throat is?' And I would say, 'It's Mark Felt.'"[4] Classmates of Jacob Bernstein at the Dalton School and Vassar College recall Jacob's revealing to numerous people that Felt was Deep Throat. Curiously, this revelation did not get any real attention from the media during the many years that the identity of Deep Throat was a mystery. Ephron later conceded that "No one, apart from my sons, believed me."[16] Ephron was invited by Arianna Huffington to write about the experience in the Huffington Post, for which she was a regular blogger and part-time editor.[15]

"Like most of my contemporaries, I first read The Fountainhead when I was 18 years old. I loved it. I too missed the point. I thought it was a book about a strong-willed architect...and his love life.... I deliberately skipped over all the passages about egoism and altruism. And I spent the next year hoping I would meet a gaunt, orange-haired architect who would rape me. Or failing that, an architect who would rape me. Or failing that, an architect. I am certain that The Fountainhead did a great deal more for architects than Architectural Forum ever dreamed." The New York Times Book Review (1968)

"...you can settle for reality, or you can go off, like a fool, and dream another dream." Heartburn

"Women are being considered as candidates for Vice President of the United States because it is the worst job in America. It's amazing that men will take it. A job with real power is First Lady. I'd be willing to run for that. As far as the men who are running for President are concerned, they aren't even people I would date." Nora Ephron, November 4, 1983, (San Francisco lecture)[23][24]

"Maybe young women don't wonder whether they can have it all any longer, but in case any of you are wondering, of course you can have it all." 1996 Wellesley commencement.[25]